Identification of Immunologic Mechanisms of Enhanced Ng Clearance Induced by Nm OMV-based Vaccines

摘要 淋球菌(Ng)是全球最流行的性传播细菌病原体，以及 淋球菌对抗生素的耐药性继续上升。潜在的无法治愈的淋病被认为是紧急的 世卫组织和美国疾控中心的威胁。淋球菌疫苗的开发对帮助阻止肺炎的传播至关重要 耐药菌株Ng.因为自然获得性感染不会导致对随后的 感染，保护免受感染所需的免疫反应从未被确定为 淋病奈瑟菌。最近，已经开发出一种针对脑膜炎奈瑟氏菌(Nm)B群和MASS的疫苗。 这种含有外膜泡(OMV)的疫苗的接种活动已经证明 淋病发病率的降低。NM-OMV疫苗在生殖器感染的小鼠模型中也显示出保护作用 NG感染。这是我们第一次有机会研究人类和小鼠对 有效的疫苗，并确定可能的保护相关因素。淋病疫苗合作社项目1 研究中心(GV CRC)将(1)确定小鼠对Nm-OMV-1的体液免疫应答 含有疫苗的疫苗在预防Ng感染方面很重要；(2)鉴定小鼠细胞免疫 含有Nm-OMV的疫苗诱导的有助于预防Ng感染的机制；以及(3) Nm-OMV疫苗诱导小鼠对Ng抗原的体液和细胞免疫应答 人类。确定提供对Ng感染的保护的免疫机制对于推动 我们将与GV CRC的所有4个科学核心进行接触。我们的研究将为 Nm-OMV疫苗预防Ng的临床评估阶段，并将为疫苗开发提供信息 其他GV CRC项目中的计划。

Abstract Neisseria gonorrhoeae (Ng) is the most prevalent sexually transmitted bacterial pathogen globally, and gonococcal antibiotic resistance continues to rise. Potentially untreatable gonorrhea is recognized as an urgent threat by WHO and the US CDC. Gonococcal vaccine development is critical to help stem the spread of antimicrobial resistant Ng. Because naturally-acquired infection does not result in immunity from subsequent infection, immune responses required for protection from infection have never been definitively established for N. gonorrhoeae. Recently, a vaccine has been developed for N. meningitidis (Nm) serogroup B, and mass vaccination campaigns with this outer membrane vesicle (OMV)-containing vaccine have demonstrated collateral reduction in gonorrhea rates. Nm-OMV vaccines also show protection in a mouse model of genital Ng infection. For the first time,we have the opportunity to study both human and murine immune responses to effective vaccines, and identify likely correlates of protection. Project 1 in the Gonorrhea Vaccine Cooperative Research Center (GV CRC) will (1) determine whether murine humoral immune responses to Nm-OMV- containing vaccines are important in protection from Ng infection; (2) identify murine cellular immune mechanisms induced by Nm-OMV-containing vaccines that contribute to protection from Ng infection; and (3) determine humoral and cellular immune responses to Ng antigens induced by Nm-OMV-containing vaccine in humans. Defining immunologic mechanisms that provide protection from Ng infection is critical to advancing Ng vaccine development.!We will engage with all 4 scientific cores of the GV CRC. Our studies will set the stage for clinical evaluation of Nm-OMV vaccines for protection from Ng and will inform vaccine development plans in other GV CRC projects.